Alkylated DNA repair protein alkB homolog 1

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Q13686 (ALKB1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 96. History...

Clusters with 100%, 90%, 50% identity |

Documents (5) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Alkylated DNA repair protein alkB homolog 1
EC=1.14.11.-

Alternative name(s):
Alpha-ketoglutarate-dependent dioxygenase ABH1
DNA lyase ABH1
EC=4.2.99.18

Gene names

Name:	ALKBH1
Synonyms:	ABH, ABH1, ALKBH

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	389 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Dioxygenase that repairs alkylated single-stranded DNA and RNA containing 3-methylcytosine by oxidative demethylation. Requires molecular oxygen, alpha-ketoglutarate and iron. May have a role in placental trophoblast lineage differentiation By similarity. Has DNA lyase activity and introduces double-stranded breaks at abasic sites. Cleaves both single-stranded DNA and double-stranded DNA at abasic sites, with the greatest activity towards double-stranded DNA with two abasic sites. DNA lyase activity does not require alpha-ketoglutarate and iron. Ref.5 Ref.6
Catalytic activity	The C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate.
Cofactor	Binds 1 Fe²⁺ ion per subunit. Ref.5
Subunit structure	Monomer. Interacts with DNAJB6 By similarity. Ref.6
Subcellular location	Mitochondrion. Nucleus By similarity. Note: Mainly localizes in euchromatin, largely excluded from heterochromatin and nucleoli By similarity. Ref.4 Ref.5
Tissue specificity	Ubiquitous. Ref.4 Ref.5
Sequence similarities	Belongs to the alkB family. Contains 1 Fe2OG dioxygenase domain.
Caution	Detected in cytoplasm and nucleus When expressed as fusion protein with an N-terminal tag, or when the first 26 N-terminal residues are removed (Ref.4 and Ref.5). The endogenous, unmodified protein localizes to mitochondria (Ref.5).
Sequence caution	The sequence CAA63047.1 differs from that shown. Reason: Frameshift at several positions.

Ontologies

Keywords
Biological process	DNA damage DNA repair RNA repair
Cellular component	Mitochondrion Nucleus
Coding sequence diversity	Polymorphism
Ligand	Iron Metal-binding
Molecular function	Dioxygenase Lyase Oxidoreductase
Technical term	Complete proteome Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological process	DNA dealkylation involved in DNA repair Inferred from direct assay Ref.5. Source: UniProtKB DNA demethylation Inferred from direct assay Ref.5. Source: UniProtKB RNA repair Inferred from direct assay Ref.5. Source: UniProtKB oxidative demethylation Inferred from direct assay Ref.5. Source: UniProtKB
Cellular component	mitochondrion Inferred from direct assay Ref.5. Source: UniProtKB
Molecular function	DNA-(apurinic or apyrimidinic site) lyase activity Inferred from direct assay Ref.6. Source: UniProtKB ferrous iron binding Inferred from direct assay Ref.5. Source: UniProtKB methylcytosine dioxygenase activity Inferred from direct assay Ref.5. Source: UniProtKB oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 389

389

Alkylated DNA repair protein alkB homolog 1

PRO_0000066668

Regions

Domain

208 – 347

140

Fe2OG dioxygenase

Region

177 – 179

Substrate binding By similarity

Region

220 – 222

Alpha-ketoglutarate binding By similarity

Region

338 – 344

Alpha-ketoglutarate binding By similarity

Sites

Metal binding

231

Iron; catalytic By similarity

Metal binding

233

Iron; catalytic By similarity

Metal binding

287

Iron; catalytic By similarity

Binding site

170

Substrate By similarity

Binding site

261

Substrate By similarity

Natural variations

Natural variant

135

M → I.
Corresponds to variant rs17825440 [ dbSNP | Ensembl ].

VAR_048221

Natural variant

324

M → L.
Corresponds to variant rs6494 [ dbSNP | Ensembl ].

VAR_048222

Experimental info

Mutagenesis

218

I → L: Reduces Fe2OG dioxygenase activity by 50%. Ref.5

Mutagenesis

231

H → A: Near loss of Fe2OG dioxygenase activity. No effect on DNA lyase activity. Ref.5 Ref.6

Mutagenesis

233

D → A: Loss of Fe2OG dioxygenase activity. No effect on DNA lyase activity. Ref.5 Ref.6

Mutagenesis

287

H → A: Loss of Fe2OG dioxygenase activity. No effect on DNA lyase activity. Ref.5 Ref.6

Mutagenesis

338

R → A: Reduced Fe2OG dioxygenase activity. Ref.5

Mutagenesis

344

R → A: Reduced Fe2OG dioxygenase activity. Ref.5

Sequence conflict

133

K → T in CAA63047. Ref.1

Sequence conflict

266 – 267

TA → PP in CAA63047. Ref.1

Sequence conflict

388

D → H in AAH25787. Ref.3

Sequences

Sequence

Length

Mass (Da)

Tools

Q13686 [UniParc].

Last modified December 1, 2000. Version 2.
Checksum: 539C4CE41D2D8AEC
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FASTA

389

43,832

        10         20         30         40         50         60 
MGKMAAAVGS VATLATEPGE DAFRKLFRFY RQSRPGTADL EGVIDFSAAH AARGKGPGAQ 

        70         80         90        100        110        120 
KVIKSQLNVS SVSEQNAYRA GLQPVSKWQA YGLKGYPGFI FIPNPFLPGY QWHWVKQCLK 

       130        140        150        160        170        180 
LYSQKPNVCN LDKHMSKEET QDLWEQSKEF LRYKEATKRR PRSLLEKLRW VTVGYHYNWD 

       190        200        210        220        230        240 
SKKYSADHYT PFPSDLGFLS EQVAAACGFE DFRAEAGILN YYRLDSTLGI HVDRSELDHS 

       250        260        270        280        290        300 
KPLLSFSFGQ SAIFLLGGLQ RDEAPTAMFM HSGDIMIMSG FSRLLNHAVP RVLPNPEGEG 

       310        320        330        340        350        360 
LPHCLEAPLP AVLPRDSMVE PCSMEDWQVC ASYLKTARVN MTVRQVLATD QNFPLEPIED 

       370        380 
EKRDISTEGF CHLDDQNSEV KRARINPDS

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and functional analysis of a human cDNA encoding an Escherichia coli AlkB homolog, a protein involved in DNA alkylation damage repair." Wei Y.F., Carter K.C., Wang R.P., Shell B.K. Nucleic Acids Res. 24:931-937(1996) [PubMed: 8600462] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Synovial sarcoma.
[2]	"The DNA sequence and analysis of human chromosome 14." Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. Weissenbach J. Nature 421:601-607(2003) [PubMed: 12508121] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Pancreas.
[4]	"Expression and sub-cellular localization of human ABH family molecules." Tsujikawa K., Koike K., Kitae K., Shinkawa A., Arima H., Suzuki T., Tsuchiya M., Makino Y., Furukawa T., Konishi N., Yamamoto H. J. Cell. Mol. Med. 11:1105-1116(2007) [PubMed: 17979886] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[5]	"Human AlkB homolog 1 is a mitochondrial protein that demethylates 3-methylcytosine in DNA and RNA." Westbye M.P., Feyzi E., Aas P.A., Vagbo C.B., Talstad V.A., Kavli B., Hagen L., Sundheim O., Akbari M., Liabakk N.B., Slupphaug G., Otterlei M., Krokan H.E. J. Biol. Chem. 283:25046-25056(2008) [PubMed: 18603530] [Abstract] Cited for: FUNCTION, COFACTOR, SUBCELLULAR LOCATION, MUTAGENESIS OF ILE-218; HIS-231; ASP-233; HIS-287; ARG-338 AND ARG-344, MASS SPECTROMETRY, TISSUE SPECIFICITY.
[6]	"Human AlkB homologue 1 (ABH1) exhibits DNA lyase activity at abasic sites." Muller T.A., Meek K., Hausinger R.P. DNA Repair 9:58-65(2010) [PubMed: 19959401] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF HIS-231; ASP-233 AND HIS-287, SUBUNIT.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X91992 mRNA. Translation: CAA63047.1. Frameshift. AC008044 Genomic DNA. Translation: AAF01478.1. BC025787 mRNA. Translation: AAH25787.1.
IPI	IPI00014482.
PIR	S64736.
RefSeq	NP_006011.2. NM_006020.2.
UniGene	Hs.94542.
3D structure databases
ProteinModelPortal	Q13686.
ModBase	Search...
Protein-protein interaction databases
STRING	Q13686.
Polymorphism databases
DMDM	12643239.
Proteomic databases
PRIDE	Q13686.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000216489; ENSP00000216489; ENSG00000100601.
GeneID	8846.
KEGG	hsa:8846.
NMPDR	fig\|9606.3.peg.9945.
UCSC	uc001xuc.1. human.
Organism-specific databases
CTD	8846.
GeneCards	GC14M078138.
H-InvDB	HIX0011855.
HGNC	HGNC:17911. ALKBH1.
MIM	605345. gene.
neXtProt	NX_Q13686.
PharmGKB	PA134906996.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG12899.
HOGENOM	HBG717273.
HOVERGEN	HBG050487.
InParanoid	Q13686.
OMA	HYNWDSK.
OrthoDB	EOG4868CJ.
PhylomeDB	Q13686.
Gene expression databases
ArrayExpress	Q13686.
Bgee	Q13686.
CleanEx	HS_ALKBH1.
Genevestigator	Q13686.
GermOnline	ENSG00000100601. Homo sapiens.
Family and domain databases
InterPro	IPR004574. Alkb. IPR005123. Oxoglutarate/Fe-dep_oxygenase. [Graphical view]
KO	K10765.
TIGRFAMs	TIGR00568. Alkb. 1 hit.
PROSITE	PS51471. FE2OG_OXY. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	33208.
SOURCE	Search...

Entry information

Entry name

ALKB1_HUMAN

Accession

Primary (citable) accession number: Q13686
Secondary accession number(s): Q8TAU1, Q9ULA7

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	December 1, 2000
Last modified:	January 25, 2012
This is version 96 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Natural variations

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Polymorphism databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents